One possible mechanism would be downregulation of mGlu2 receptors. These receptors generally are located on glutamatergic neurons and act as a form of negative feedback in response to synaptic glutamate release. Astrocytes help regulate synaptic glutamate release via their expression of cystine-glutamate transporters, which import a molecule of cystine in exchange for releasing a molecule of glutamate extrasynaptically. This extrasynaptic glutamate binds to mGlu2 receptors and inhibits synaptic glutamate release.
With NAC you increase the extracellular concentration of cystine which in turn increases the release of extrasynaptic glutamate (essentially due to Le Chatelier's principle). This will produce a tonic increase in mGlu2 signaling which could lead to mGlu2 downregulation/desensitization, which would in turn make these glutamatergic neurons more excitable. This is the most convincing approach I've thought of for reversing dissociative tolerance, since acute NAC inhibits the effects of dissociatives by activating mGlu2 receptors on the thalamocortical tracts which dissociatives excite (and downregulation/desensitization of these mGlu2 receptors would facilitate thalamocortical disinhibition in the absence of NAC). Whether this mechanism could account for perceived reductions in MDMA tolerance is anyone's guess, but being a quite general mechanism it's within the realm of possibility.
What does seem completely unlikely, is that NAC would reverse epigenetic changes which erase the molecular pathways responsible for the MDMA high in drug-naive individuals. For example, the high intracellular concentrations of 5-HT produced by MDMA could lead to significant serotonylation (i.e. the incorporation of 5-HT into various proteins via covalent bonds). This is an understudied area but it's known that serotonylation can constitutively activate small G proteins or alter transcription (via its incorporation into histone proteins).
Another higher-level way of looking at drug tolerance is that the experience is no longer novel. It's really no different than a song becoming boring after listening to it a bunch, even though it used to blow your mind. Once you have enough autobiographical memories in regard to what a certain experience is like, it becomes predictable. One important mediator of autobiographical memory is the DMN, which is acutely disintegrated by psychedelic drugs. So perhaps a psychedelic would be a good pre-roll supplement to temporarily reduce your access to the information regarding your MDMA experiences and make the experience less predictable. And not even a full trip necessarily, I've found that even with the smallest hits off of a DMT cartridge, I can go outside and it's like looking at the world with fresh eyes again. Mediation also generally weakens the DMN, especially with long-term practice, so that's something worth looking into as well.
